Comprehensive analysis of microarray expression profiles of circRNAs and lncRNAs with associated co-expression networks in human colorectal cancer

Abstract

Increasing data demonstrate that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) play important roles in tumorigenesis. However, the mechanisms in colorectal cancer (CRC) remain unclear. Here, hundreds of significantly expressed circRNAs, and thousands of lncRNAs as well as mRNAs were identified. By qRT-PCR, one abnormal circRNA, lncRNA, and three mRNAs were verified in 24 pairs of tissues and blood samples, respectively. Then, by GO analysis, we found that the gene expression profile of linear counterparts of upregulated circRNAs in human CRC tissues preferred positive regulation of GTPase activity, cellular protein metabolic process, and protein binding, while that of downregulated circRNAs of CRC preferred positive regulation of cellular metabolic process, acetyl-CoA metabolic process, and protein kinase C activity. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that p53 signaling pathway was an important pathway in upregulated protein-coding genes, whereas cyclic guanosine monophosphate-protein kinase G (cGMP–PKG) signaling pathway was the top enriched KEGG pathway for downregulated transcripts. Furthermore, lncRNA–mRNA co-expression analysis demonstrated that downregulated lncRNA uc001tma.3 was negatively with CDC45 and positively with ELOVL4, BVES, FLNA, and HSPB8, while upregulated lncRNA NR_110882 was positively with FZD2. In addition, lncRNA–transcription factor (TF) co-expression analysis showed that the most relevant TFs were forkhead box protein A1 (FOXA1), transcription initiation factor TFIID submint 7 (TAF7), and adenovirus early region 1A(E1A)-associated protein p300 (EP300). Our findings offer a fresh view on circRNAs and lncRNAs and provide the foundation for further study on the potential roles of circRNAs and lncRNAs in colorectal cancer. Electronic supplementary material The online version of this article (10.1007/s10142-018-0641-9) contains supplementary material, which is available to authorized users.

Circular RNAs: A New Piece in the Colorectal Cancer Puzzle

“…This phenomenon seems to be independent of the expression tendencies of single circRNAs and linear transcripts, while the aforementioned ratio and the cell proliferation index are inversely associated [ 42 ]. The same tendency has also been observed in other research studies [ 43 , 44 ]. Interestingly, following the comparison of circRNA expression profiles among CRC cell lines with distinct KRAS mutational status, Dou et al demonstrated that circRNA expression levels in KRAS -mutated cells are significantly lower than in the KRAS -wild type cells, while they showed that circRNAs can be transferred to exosomes, where they are abundant [ 45 ].…”

Circular RNA Expression Profiling and the Potential Role of hsa_circ_0089172 in Hashimoto’s Thyroiditis via Sponging miR125a-3p

“…They could competitively bind to the miRNA and then decrease the inhibitory effect of the miRNA on the expression of target genes 23, 24. Many studies have proved that circRNAs are potential biomarkers and participate in pathogenesis of various autoimmune diseases 25, 26, 27. For instance, decreased hsa_circ_0044235 in PBMCs has been confirmed to have significant value in the diagnosis of RA.…”

Comprehensive Analysis of Differentially Expressed circRNAs Reveals a Colorectal Cancer-Related ceRNA Network

“…Newly generated researches showed that noncoding RNAs displayed importance in carcinogenesis and cancer development [ 51 ]. Some reports have shown that circRNAs displayed importance in the process of biology and the progression of diseases through sponging miRNA [ 13 , 14 ]. For example, circular RNA Circ100084, exhibiting as the sponge of miR-23a-5p, modulated the expression of IGF2 in hepatocarcinoma [ 52 ].…”

“…Currently, some researches had shown that circRNAs modulated alternative splicing and gene expression level through sponging microRNAs (miRNAs) [ 11 , 12 ]. At the same time, disorders of circRNAs took part in carcinogenesis and cancer development of CRC [ 13 , 14 ], liver cancer [ 15 ], and gastric cancer [ 16 – 19 ]. These findings indicated that circRNAs, as a new kind of endogenous noncoding RNA, have been a new hotspot in the cancer research and probably would exhibit important functions in the development of tumor.…”